Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E<sub>2</sub>/ER<italic style="font-style: italic">β</italic> Signaling Pathway

Hong-dan XU; Qi QIU; Yan-qiu DU; Shuang LIU; Shu-ming HUANG

doi:10.13422/j.cnki.syfjx.20211903

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Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E₂/ERβ Signaling Pathway

更新时间：2021-10-14

- Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E₂/ERβ Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 21, Pages: 10-18(2021)
- 作者机构：
  
  1.黑龙江中医药大学佳木斯学院，黑龙江佳木斯 154007
  2.黑龙江中医药大学中药学博士后流动站，哈尔滨 150040
  3.黑龙江中医药大学药学院，哈尔滨 150040
  4.黑龙江中医药大学中医药研究院，哈尔滨 150040
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211903
  CLC： R2-0;R22;R285.5;R289;R33
- Received：03 July 2021，
  
  Published Online：12 August 2021，
  
  Published：05 November 2021
- 稿件说明：
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徐红丹,邱琦,杜艳秋等.E₂/ERβ信号通路介导引火汤改善慢性应激诱导的双侧卵巢摘除小鼠抑郁样行为[J].中国实验方剂学杂志,2021,27(21):10-18.

XU Hong-dan,QIU Qi,DU Yan-qiu,et al.Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E₂/ERβ Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):10-18.
徐红丹,邱琦,杜艳秋等.E₂/ERβ信号通路介导引火汤改善慢性应激诱导的双侧卵巢摘除小鼠抑郁样行为[J].中国实验方剂学杂志,2021,27(21):10-18. DOI： 10.13422/j.cnki.syfjx.20211903.

XU Hong-dan,QIU Qi,DU Yan-qiu,et al.Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E₂/ERβ Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):10-18. DOI： 10.13422/j.cnki.syfjx.20211903.

摘要

目的

观察引火汤（YHT）对慢性应激诱导的双侧卵巢摘除（OVX）小鼠抑郁样行为的影响并探索其基于雌二醇（E

）/雌激素受体

（ER

）信号通路的作用机制。

方法

实验分两部分完成，第一部分将小鼠随机分为假手术组（Sham），模型组（OVX），阳性药组（E

，0.13 mg·kg

-1

）和引火汤组（YHT，23.4 g·kg

-1

）。采用OVX联合慢性不可预知性温和刺激（CUMS）方法复制OVX。双侧卵巢摘除术后第8天，各组小鼠开始CUMS并开始给药，强迫游泳（FST），悬尾（TST），旷场（OFT）3种行为学实验观察各组小鼠不动时间、水平运动评分及垂直运动评分变化，酶联免疫吸附测定法（ELISA）检测血清、脑组织E

水平，实时荧光定量聚合酶链式反应（Real-time PCR）检测芳香化酶（Cyp19）基因转录，免疫组织化学法（IHC）检测海马齿状回ER

和ER

表达，蛋白免疫印迹法（Western blot）检测脑内总ER

和ER

蛋白水平。第二部分实验分Sham，OVX，YHT和阻断剂组（Y+B，23.4 g·kg

-1

+100 μg·kg

-1

），Y+B组小鼠在引火汤灌胃同时采用隔天腹腔注射方式的给予ER

阻断剂（PHTPP），3种行为学实验观察各组小鼠不动时间、水平运动评分及垂直运动评分变化。

结果

与Sham组比较，OVX组小鼠不动时间显著增加、水平运动及垂直运动水平显著降低（

0.01），血清和脑内E

显著降低（

0.01），脑内Cyp19 mRNA表达显著降低（

0.01），海马齿状回和脑内总ER

差异无统计学意义，海马齿状回和脑内总ER

表达显著降低（

0.01）；与OVX组比较，E

组小鼠不动时间显著降低、水平运动及垂直运动水平显著增加（

0.01），血清E

显著升高（

0.01），脑内Cyp19 mRNA表达差异无统计学意义，海马齿状回和脑内总ER

差异无统计学意义，海马齿状回和脑内总ER

表达显著升高（

0.01），YHT组小鼠不动时间显著降低、水平运动及垂直运动水平显著增加（

0.01），血清E

未见升高，脑内E

明显升高（

0.01），脑内Cyp19 mRNA表达显著增加（

0.01），海马齿状回和脑内总ER

差异无统计学意义，海马齿状回和脑内总ER

表达均显著升高（

0.05，

0.01）。PHTPP可阻断引火汤对OVX小鼠在FST，TST，OFT实验中的作用。

结论

引火汤促进脑内源性雌激素合成和释放，激活E

/ER

信号通路可能是其改善慢性应激诱导的OVX小鼠抑郁样行为关键机制之一。

Abstract

Objective

To observe the effect of Yinhuotang （YHT） on the depression-like behavior of mice with bilateral ovariectomy （OVX） induced by chronic stress and explore its action mechanism based on estradiol （E

）-estrogen receptor

（ER

） pathway.

Method

The experiment was divided into two parts. In the first part， mice were randomly divided into the sham operation （Sham） group， model （OVX） group， positive drug （E

， 0.13 mg·kg

-1

） group， and YHT （23.4 g·kg

-1

） group. The OVX model was reproduced by OVX combined with chronic unpredictable mild stress （CUMS）. On the 8th day after OVX， the mice in each group were exposed to CUMS and treated with drugs. The changes in immobility time， horizontal movement score， and vertical movement score of mice in each group were observed in forced swimming test （FST）， tail suspension test （TST） and open-field test （OFT）， respectively. Serum and brain E

levels were detected by enzyme-linked immunosorbent assay （ELISA）， the aromatizing enzyme （Cyp19） mRNA expression by real-time fluorescence polymerase chain reaction （Real-time PCR）， the expression of ER

and ER

in dentate gyrus of hippocampus by immunohistochemistry （IHC）， and the total ER

and ER

levels in the brain by Western blotting. In the second part， the mice were divided into the Sham group， OVX group， YHT group， and blocker （Y+B， 23.4 g·kg

-1

+100 μg·kg

-1

） group. Mice in the Y+B group were first treated with intragastric administration of YHT and then with intraperitoneal injection of ER

blocker （PHTPP） on the next day. The changes in immobility time， horizontal motor score， and vertical motor score were observed in the three behavioral tests.

Result

Compared with the Sham group， the OVX group displayed significantly increased immobility time， decreased horizontal and vertical movement scores （

0.01）， down-regulated serum and brain E

levels （

0.01） and Cyp19 mRNA expression in the brain （

0.01）， and up-regulated total ER

in dentate gyrus and brain （

0.01）. However， there was no significant change in total ER

expression in the dentate gyrus or brain. As revealed by comparison with the OVX group， the immobility time of the E

group was decreased significantly， while the horizontal and vertical movement scores were increased significantly （

0.01）. The E

levels in the serum was significantly elevated （

0.01）. The Cyp19 mRNA expression in the brain and the total ER

expression in the dentate gyrus and brain were not significantly changed， while the expression levels of total ER

in dentate gyrus and brain were significantly increased （

0.01）. In the YHT group， the immobility time declined significantly， and the horizontal and vertical movement scores rose significantly （

0.01）. The serum E

did not increase， whereas the brain E

increased significantly （

0.01）. The expression of Cyp19 gene in the brain was significantly increased （

0.05，

0.01）. There was no significant change in the total ER

of dentate gyrus and brain， but the expression levels of total ER

in dentate gyrus and brain were significantly increased （

0.05，

0.01）. PHTPP reversed the effects of YHT on OVX mice in FST， TST and OFT.

Conclusion

YHT promotes the synthesis and release of endogenous estrogen in brain and improves the depression-like behavior of OVX mice induced by chronic stress， which is possibly related to the activation of E

/ER

pathway.

关键词

Keywords

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⁰

Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E2/ERβ Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20211903

摘要

Abstract

关键词

Keywords

references

Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E₂/ERβ Signaling Pathway